There is ample evidence showing that the stress of caring for a relative with Alzheimer's Disease (AD) adversely affects caregivers. Data from our longitudinal study have shown that caregivers have substantially higher rates of syndromal depressive disorders than controls. Caregivers also have poorer immune function on qualitative immunological assays, and more infectious disease episodes (primarily respiratory tract infections) than noncaregivers. Spousal caregivers' immune function has not returned to the level of well-matched control subjects across the four years of the study completed thus far; moreover, bereaved spousal caregivers do not differ significantly from "continuous" caregivers on immune function or depression after bereavement. In fact, our data suggest that spousal caregivers continue to show immunological down-regulation as well as increased risk for syndromal depressive disorders for at least two years after bereavement. The persistent immunological down-regulation associated with caregiving is of particular concern because aged individuals already have diminished immune function, and these age-related reductions have important health consequences: vaccine seroconversion in aged individuals is problematic, and respiratory viral infections such as influenza are a major cause of morbidity and mortality. In this grant we propose to provide free annual flu vaccinations for 5 years for our ongoing cohort of 110 spousal caregivers (including both bereaved and continuing caregivers) and 90 controls. We will examine the relationships between caregiving-related stresses and other psychosocial variables and degree of immune reactivity and immunological memory to the annual vaccinations. These data will provide a direct, in vivo assessment of the modulation of immune function by chronic stress, with obvious and important health implications for older adults.